Despite the known correlation between estrogens and carcinogenesis, estrogen replacement therapy remains the number one treatment for menopausal symptoms. Cimicifuga racemosa is a rhizome that has been proven effective in reducing hot flashes in several clinical trials. The exact mechanism of action of the herb remains unknown. Studies may reveal that the plant works by modulating serotonin levels and thereby reduces hot flashes. If the plant ameliorates hot flashes without increasing estradiol levels, the botanical will provide a safe and effective solution for women with a history of breast cancer. The focus of this proposal is to train the applicant how to research botanicals by investigating the mechanism of Cimicifuga racemosa. The specific aims are (I.) to identify the active componant(s) of the plant using competitive serotonin receptor binding assays. (II.) Cellular in vitro studies will be conducted to determine the herbs agonistic or antagonistic properties, to establish and quantify serotonin subtype binding specificity, to characterize up- or down-regulation of receptor, and to monitor the serotonin dependent excretion of gonadotropic releasing hormones. (III.) Finally, an ovariectomized rat model will be used to evaluate the serotonergic effects of extracts and compounds in vivo.